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Published on: April 1, 2019
NAT2 slow acetylator associated with anti-tuberculosis drug-induced liver injury in Thai patients
S Wattanapokayakit1, T Mushiroda2, H Yanai3
1Medical Genetics Center, Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Background:
Anti-tuberculosis drug-induced liver injury (AT-DILI) is one of the most common forms of drug-induced liver injury (DILI) in high tuberculosis (TB) burden countries. Among anti-tuberculosis drugs, isoniazid is the main cause of hepatotoxicity in patients with AT-DILI.
Objective:
To investigate the association of AT-DILI with N-acetyltransferase 2 (NAT2) genotype status in Thai TB patients.
Methods:
We enrolled 53 patients diagnosed with AT-DILI and 85 patients who tolerated anti-tuberculosis treatment as controls. Acetylator status was determined based on the inferred NAT2 haplotypes from four common single-nucleotide polymorphisms (SNPs) in Thais using Sanger sequencing.
Results:
Phenotype frequencies of the NAT2 acetylator in AT-DILI patients were respectively 71.7%, 22.6% and 5.7% for slow, intermediate and rapid acetylators. Among slow, intermediate, and rapid acetylators in treatment tolerant controls, phenotype frequencies were respectively 22.4%, 62.4% and 15.3%. Slow NAT2 acetylators demonstrated a significant association with risk of AT-DILI. The odds ratio of comparing slow NAT2 acetylator in DILI patients and tolerance was 8.80 (95%CI 4.01-19.31, P = 1.53 × 10-8).
Conclusions:
Slow acetylator status in the NAT2 genotype is a significant risk factor for DILI in Thai patients with TB. This evidence provides confirmatory data in support of the role of NAT2 in AT-DILI in the Thai population.
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